Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of severe aortic stenosis, particularly in high-risk surgical patients or those deemed inoperable. However, this technique is not without complications, one of the most significant being TAVI thrombosis, which poses considerable diagnostic and therapeutic challenges. TAVI thrombosis encompasses a spectrum ranging from subclinical leaflet thrombosis (SLT) to clinical valve thrombosis (CVT). 

In this article, the group led by Adrichem et al. reviews randomized clinical trials, observational studies, and retrospective analyses evaluating various therapeutic strategies for managing TAVI thrombosis. The interventions addressed include vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), thrombolytic therapy, and reintervention/surgery. 

SLT is characterized by leaflet thickening (hypoattenuated leaflet thickening, HALT) and reduced leaflet motion (RLM). It occurs in approximately 12% to 38% of patients within 30 days post-TAVI and is often an incidental finding during multislice computed tomography (MSCT), as the spatial resolution of transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) is generally insufficient to detect HALT and/or RLM. Studies have shown that between 35% and 54% of HALT cases observed at 30 days resolve spontaneously within a year without changes in the antithrombotic regimen. Conversely, 15% to 20% of HALT cases progress to RLM, and 3% to 9% advance to clinical valve thrombosis (CVT) with manifest symptoms. Although the clinical implications of SLT are not always clear, it has been associated with increased transvalvular gradients, embolic events, and, in some cases, structural valve degeneration. 

Clinical thrombosis (CVT) is less common (estimated global incidence 1.2%) but potentially fatal, as it may lead to severe valve insufficiency, heart failure, thromboembolic events, and, ultimately, death. Most CVT cases are reported during the first year post-TAVI, whereas structural valve degeneration predominantly occurs after the first year. In CVT management, normalization of transprosthetic gradients to levels recorded immediately after the initial TAVI procedure may suffice to monitor resolution. 

The authors provide practical guidelines for the clinical management of both phenomena: 

• Management of TAVI SLT:
  The authors highlight how VKAs and DOACs are associated with a lower incidence of HALT and RLM, advocating for a shift from antiplatelet therapy (single or dual) to a VKA- or DOAC-based regimen to treat HALT and RLM when they occur. However, it is important to note that prophylactic use of DOACs after TAVI in patients without a formal indication is contraindicated. Both the GALILEO and ATLANTIS trials showed that combining DOACs with antiplatelet therapy resulted in higher rates of bleeding and all-cause mortality, thus this combination should be reserved for cases without resolution using monotherapy with VKA/DOAC. For monitoring resolution, close follow-up with clinical evaluation and TTE imaging is recommended for patients with confirmed HALT. Optional MSCT follow-up at 3–6 months can assess HALT resolution. 

• Management of TAVI CVT:
  Switching to oral anticoagulation is recommended for patients who develop CVT while on antiplatelet therapy. For those with CVT under DOAC therapy, switching to a VKA is advised, as no direct comparisons between different DOACs support switching from one to another. Heparin may be used temporarily until therapeutic INR levels are achieved. After confirming CVT resolution through MSCT and/or normalization of transprosthetic gradients to levels immediately post-TAVI, oral anticoagulation may be discontinued. However, the article highlights frequent recurrences, suggesting follow-up MSCT at 6 months after discontinuing anticoagulation and considering indefinite therapy with VKAs or DOACs in the absence of bleeding complications.
  For refractory TAVI CVT cases, slow infusion of low-dose alteplase (25 mg over 25 hours) demonstrated the highest success rates (90%) with few complications, proving effective and safe while avoiding explant or surgical reintervention. Explant surgery in the context of valve thrombosis is a high-risk procedure, as shown in the EXPLANT TAVR registry, which reported 30-day mortality and stroke rates of 13.1% and 6%, respectively. Conversely, redo-TAVI had lower 30-day complication rates, with mortality and stroke rates of 2.9% and 1.4%, respectively. 

COMMENTARY:

Although SLT does not always manifest with symptoms or hemodynamic dysfunction, its association with transient neurological events and long-term valve degeneration underscores its clinical relevance. The proposed echocardiographic and MSCT follow-up should be essential; however, its widespread implementation is limited by associated costs and routine availability of these techniques. Additionally, the dilemma between efficacy and safety in anticoagulant selection remains challenging. VKAs, while effective, require intensive and periodic INR monitoring, which can be a barrier for elderly patients or those with multiple comorbidities. On the other hand, DOACs, theoretically more convenient, have shown mixed results in terms of safety, especially when combined with antiplatelets, emphasizing the need to individualize treatment by considering factors such as frailty and bleeding history. 

Low-dose slow thrombolysis can be considered in patients with refractory CVT, but current data remain limited to small populations. Randomized trials with larger sample sizes comparing this strategy with other interventions, such as surgical reintervention or other intensive pharmacological strategies, would be beneficial. Furthermore, the article highlights the risks associated with explant surgery in TAVI patients, supporting the preference for redo-TAVI in selected cases. 

Evaluating each case collectively within the Heart Team and informing patients about the benefits and risks of each treatment strategy is reasonable to provide the most adequate and personalized treatment. From a practical standpoint, the following considerations can be made: 

1. In the absence of a formal anticoagulation indication, VKAs or DOACs are not recommended after TAVI implantation to prevent SLT and/or CVT. 
2. If SLT is identified in a patient on antiplatelet therapy, follow-up with TTE/MSCT at 3–6 months is recommended. If evolution toward CVT is observed, switching from antiplatelet therapy to VKAs or DOACs (preferably VKAs) is advised. If DOACs are chosen and there is no resolution of CVT after 3–6 months, a switch from DOACs to VKAs should be considered. If CVT resolves with this regimen and there is no high bleeding risk, indefinite use of DOACs/VKAs can be considered. 
3. If CVT persists or progresses despite treatment with VKAs or DOACs, adding antiplatelet therapy is recommended. If CVT resolves with this regimen and bleeding risk is low, indefinite use of DOACs/VKAs + antiplatelets can be considered. 
4. If CVT persists or progresses despite treatment with VKAs/DOACs + antiplatelets, consideration should be given to adding the ultraslow, low-dose alteplase infusion strategy (preferably) and/or valve replacement options (redo-TAVI in selected cases, preferably over surgery). If CVT resolves with this regimen and there is no high bleeding risk, indefinite use of DOACs/VKAs +/- antiplatelets can be considered. 

 REFERENCE:

Adrichem R, Rodes Cabau J, Mehran R, Park DW, Ten Berg JM, de Backer O, et al. Treatment of Transcatheter Aortic Valve Thrombosis: JACC Review Topic of the Week. J Am Coll Cardiol. 2024 Aug 27;84(9):848-861. doi: 10.1016/j.jacc.2024.05.064.